Study procedures
An institutional clinical database was utilized to capture study data
and included evaluations for transfusional hemosiderosis with initial
MRI and contemporaneous measurements of serum iron, total iron binding
concentration (TIBC), transferrin saturation, and ferritin. Subsequent
MRI evaluations, initiation and/or adjustments in therapy with chelation
or phlebotomy were also collected. Data regarding the patients’ cancer
type, date of diagnosis, requirement of hematopoietic stem cell
transplant (HSCT), as well as adverse outcomes including relapse and/or
death were also collected. Subjects were categorized by cancer therapy
using the validated Intensity of Treatment Rating Scale
(ITR-3).13
Measures of siderosis using MRI were collected using gradient echo and
spin echo pulse sequences on 1.5 Tesla magnets. The relaxation rates R2
and R2* were estimated using custom Matlab routines, where R2 and R2*
are the reciprocals of T2 and T2*, respectively. Liver R2* was converted
to liver iron concentration (LIC) using the calibration by Wood et
al.14 Severity of LIC, pancreatic R2*, and cardiac T2*
were determined by predefined clinically important
thresholds.15-17 LIC by MRI18 was
defined as mild (LIC 3 to <7 mg/g), moderate (7 to
<15 mg/g), and severe (15 mg/g or greater). Pancreatic R2*
from 27 to <100 Hz was considered mild to moderate and 100 Hz
or greater indicated severe pancreatic siderosis based on association of
R2* > 100 with cardiac siderosis and abnormal glucose
metabolism.19 Cardiac T2* 20-30 ms was defined as
borderline, while T2*< 20 ms indicated cardiac siderosis.
Severity of pituitary siderosis was determined by predefined thresholds
of R2 values converted to Z-scores, where Z ≥ 2 was considered
clinically significant. Pituitary volume in the anterior and posterior
planes was also converted to Z-scores, where Z ≤ -2 was consistent with
volume loss.20,21 These pituitary parameters have been
related to the risk of clinical hypogonadism in thalassemia
patients.22